When this is all over, he told me, and someone has produced a way to rejuvenate a mouse, he is retiring to Madagascar.
“Madagascar?”
“I’ve had quite enough of this, I can assure you.”
I remember when I first came across Aubrey’s extraordinary name. I read a little squib about him on the Web—one of his first pieces of publicity. I sent him an e-mail, he wrote back more or less instantly, and soon there he was in my office chair, beer bottle in hand, telling me that we could live forever.
I warned Aubrey that I did not find his ideas completely kosher. I said it that day and many times thereafter. On the road to Ravenna he looked so much like Jesus, loping along, that I reminded him I wasn’t a disciple, that he and I were not of the same faith. I quoted one of my father’s Yiddish proverbs. “Az mih esst chazer, luzz rinnen ueber dem boord!” If you’re going to eat pork, let it dribble over your beard.
That’s why I was talking with him and not with a conventional gerontologist, I said.
Aubrey laughed. “In for a penny, in for a pound,” he said. “Jolly good.”
Aubrey said I was crazy to doubt him—either crazy, or a lightweight. Sometimes at the Eagle the very sight of me seemed to exasperate him as I sat there smiling in my strained, coffee-stained sobriety. “It’s just bizarre!” he would cry, like a lawyer at the bench, with a somewhat practiced indignation, his hands flying upward and his voice rising half an octave. “It’s brainwashing! What other explanation is there?”
Meanwhile, from a stool at the far end of the bar, that old Cambridge codger kept staring at our table, the man with the fixed leer from the Mad Hatter’s tea party, as if to say: You fools will never make sense. Whatever it is you are talking about, you will never make sense.
I still do not expect to see our last night’s day, that dawn when immortality shall be unveiled, to the cry of the peacocks. I think our last talk in the Eagle was the moment when that was settled between us.
“I know a lot more about biology than you do,” Aubrey declared, very stiffly, with the late afternoon sun casting those apocalyptic shafts of light onto his face. “So any conclusions based on that assumption are just illogical. You’re preferring your own uninformed speculations as a nonbiologist to mine.”
And yet, now that the journey is over, I’m surprised to find myself wavering. Maybe I’m half of the devil’s party without knowing it.
One of my best memories of Aubrey is the brief walk we took after we had paid and left the pub, debating on the cobbles and old flagstones. Aubrey showed me Trinity Hall, where he went to school, where he learned to punt, and where the ladder that led down to the river used to lean. He apologized for being so hard on me back at the Eagle. We agreed to disagree. He walked me partway to the train station through the English summer drizzle.
“Best of luck.”
After we said our goodbyes, Aubrey sprinted off. He was late for dinner with Adelaide; he’d promised to be back at seven. He flew home down that old stone street like a schoolboy of twelve.
Notes on Sources and Further Reading
“The subject is really an enormous subject,” William James wrote in 1898, in his essay “Human Immortality.” “At the back of Mr. Alger’s Critical History of the Doctrine of a Future Life there is a bibliography of more than five thousand titles of books in which it is treated.”
On top of that enormous subject, we now have the modern science of longevity. If you search for the keyword “gerontology” in the world’s largest online index of medical literature, Medline, you get a list of more than 25,000 articles, all published since the year 1950.
Of course, longevity and immortality are not the same thing. Even if gerontologists learned to slow, stop, or even reverse the process of aging, they would not make human bodies live forever. They would eliminate only one cause of death. Nevertheless, aging is by far the most common cause of death in this vale of tears. A cure for aging would mean so many centuries or millennia of future life that the prospect looks very much like immortality from here.
Because the science of longevity is so young and turbulent, it’s too soon for critical histories and giant bibliographies. Here are a few notes on some of my sources, chapter by chapter, with suggestions for further reading.
CHAPTER 1: IMMORTAL LONGINGS
In the last decade or so, as their field has heated up, gerontologists have published a whole shelf of books for a general audience. These include:
Austad, S. N. (1999). Why We Age: What Science Is Discovering About the Body’s Journey Through Life. Wiley.
Butler, R. N. (2008). The Longevity Revolution: The Benefits and Challenges of Living a Long Life. PublicAffairs.
Carnes, B. A., and S. J. Olshansky (2002). The Quest for Immortality: Science at the Frontiers of Aging. Norton.
Guarente, L. (2002). Ageless Quest: One Scientist’s Search for the Genes That Prolong Youth. Cold Spring Harbor Laboratory Press.
Hayflick, L. (1994). How and Why We Age. Ballantine.
Kirkwood, T. (1999). Time of Our Lives: The Science of Human Aging. Oxford University Press.
Rose, M. R. (2005). The Long Tomorrow: How Advances in Evolutionary Biology Can Help Us Postpone Aging. Oxford University Press.
West, M. (2003). The Immortal Cell: One Scientist’s Quest to Solve the Mystery of Human Aging. Doubleday.
Aubrey de Grey has published a book about his “Strategies for Negligible Senescence”:
de Grey, A. D. N. J., with Michael Rae (2007). Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime. St. Martin’s.
Aubrey de Grey has also published almost one hundred manifestos and scientific articles on the subject. For one of the early, provocative papers in which he rode out to battle against most gerontologists, see de Grey, A. D., B. N. Ames, et al. (2002). “Time to talk SENS: Critiquing the immutability of human aging.” Ann N Y Acad Sci 959: 452–62; discussion 463–65. As de Grey and his coauthors write, “Aging is a three-stage process: metabolism, damage, and pathology. The biochemical processes that sustain life generate toxins as an intrinsic side effect. These toxins cause damage, of which a small proportion cannot be removed by any endogenous repair process and thus accumulates.” Finding ways to remove the accumulating damage, they argue, “would sever the link between metabolism and pathology, and so has the potential to postpone aging indefinitely…. Such ways exist in all cases, implying that indefinite postponement of aging—which we term ‘engineered negligible senescence’—may be within sight.”
See also:
de Grey, A. D., J. W. Baynes, et al. (2002). “Is human aging still mysterious enough to be left only to scientists?” Bioessays 24(7): 667–76.
de Grey, A. D. (2003). “An engineer’s approach to the development of real anti-aging medicine.” Sci Aging Knowledge Environ 2003(1): VP1.
de Grey, A. D. (2004). “Biogerontologists’ duty to discuss timescales publicly.” Ann N Y Acad Sci 1019: 542–45.
de Grey, A. D. “Resistance to debate on how to postpone ageing is delaying progress and costing lives.” EMBO Rep 2005; 6:S49–S53.
For an angry counterattack by gerontologists, see:
Warner, H., J. Anderson, et al. (2005). “Science fact and the SENS agenda: What can we reasonably expect from ageing research?” EMBO Rep: 26:1006–8.
For de Grey’s defense, see these papers, and their references: de Grey, A. D. (2006). “Is SENS a farrago?” Rejuvenation Res 9(4): 436–39; de Grey, A. D. (2006). “SENS survives the challenge: Now let’s get to work.” Rejuvenation Res 9(4): 429–30.
Among dozens of recent technical reviews of current gerontology, I found this one particularly useful as a balanced guide to the literature: Vijg, J., and J. Campisi (2008). “Puzzles, promises and a cure for ageing.” Nature 454(7208): 1065–71. Vijg and Campisi survey recent discoveries in the science of aging, which seem to show that the life span of yeast, worms, flies, and mice “is plastic and can be manipulated.” The aut
hors caution that we need to understand those studies much more deeply “before we can evaluate if abrogation of human senescence is a realistic prospect.”
On the history of human longevity, I found these books helpful, among others:
Riley, J. C. (2001). Rising Life Expectancy: A Global History. Cambridge University Press.
Anderson, M. (1996). British Population History. Cambridge University Press.
The owners of the Eagle are justly proud of its history, and there are many plaques in the pub. John Chainey’s notes on the RAF graffiti are detailed and extensive.
I also consulted a few books about the town’s history, including:
Darby, H. C. (1977). Medieval Cambridgeshire. Oleander.
Cobban, A. B. (1988). The Medieval English Universities: Oxford and Cambridge to circa 1500. Scholar.
Blair, J. (1984). The Anglo-Saxon Age: A Very Short Introduction. Oxford University Press.
CHAPTER 2: THE PROBLEM OF MORTALITY
These are two good panoramic surveys of the subject’s history:
Gruman, G. J. (1966). A History of Ideas About the Prolongation of Life. Springer.
Hancock, D. B. (2009). Mortal Coil: A Short History of Living Longer. Yale University Press.
For a wise short review, read:
Shapin, S., and C. Martyn (2000). “How to live forever: Lessons of history.” BMJ 321: 1580–82.
An excellent book about Gilgamesh:
Damrosch, D. (2007). The Buried Book: The Loss and Rediscovery of the Great Epic of Gilgamesh. Holt.
On Steinach:
Wyndham, D. (2003). “Versemaking and lovemaking—W. B. Yeats’ ‘Strange Second Puberty’: Norman Haire and the Steinach rejuvenation operation.” Journal of History of the Behavioral Sciences 39(1): 25–50.
I’ve mentioned only a few twentieth-century immortalists in this chapter. If you dig down into any decade, you can find a dozen now forgotten doctors and biologists who hoped to live forever. A few months ago I found an old, slightly pulpy, but entertaining paperback: McGrady, P. M., Jr. (1968). The Youth Doctors. Ace. It is full of names of lost immortalists, including one rebel whose polemics have at least a family resemblance to Aubrey de Grey’s.
See also Comfort, A. The Process of Ageing (1964). Signet Science Library. Dated, but still good reading.
Another readable paperback from that time, also with yellowing pages:
Harrington, A. (1969). The Immortalist: An Approach to the Engineering of Man’s Divinity. Avon. It begins, “Death is an imposition on the human race, and no longer acceptable.”
CHAPTER 3: LIFE AND DEATH OF A CELL
Here are a few books about the beauty of the beginning of the life cycle:
Bonner, J. T. (1993). Life Cycles: Reflections of an Evolutionary Biologist. Princeton University Press. John Tyler Bonner, born in 1920 and still going strong, is one of the best biologist-writers alive. This is a delightful book about the evolution of the life cycle, and the evolution of Bonner.
Gilbert, S. F. (2006). Developmental Biology. Sinauer. The standard textbook.
Wolpert, L. (1991). The Triumph of the Embryo. Oxford University Press.
On the evolution of multicellular life:
Bonner, J. T. (2000). First Signals: The Evolution of Multicellular Development. Princeton University Press.
Buss, L. W. (1987). The Evolution of Individuality. Princeton University Press. A bit old, and difficult, but fascinating.
This monumental work of scholarship helped bring new life to the science of gerontology:
Finch, C. E. (1990). Longevity, Senescence, and the Genome. University of Chicago Press.
On the hydra:
Martinez, D. E. (1998). “Mortality patterns suggest lack of senescence in hydra.” Exp Gerontol 33: 217–25.
Maria Rudzinska was working in a long tradition at Rockefeller University. Not only was Alex Carrel there before her, so was another early eminence there, Jacques Loeb. See, for instance:
Loeb, J., and J. H. Northrup (1917). “On the influence of food and temperature upon the duration of life.” Biological Chem. 32: 103–21.
Two of Rudzinska’s papers on her beloved Tokophrya:
Rudzinska, M. A. (1951). “The influence of amount of food on the reproduction rate and longevity of a suctorian (Tokophrya infusionum).” Science 113: 10–11.
Rudzinska, M. A. (1984). “Cellular and clonal aging in the suctorian protozoan Tokophrya infusionum.” S. J. Karakashian, H. N. Lanners, and M. A. Rudzinska. Mech. Ageing Develop. 26: 217–29.
CHAPTER 4: INTO THE NEST OF THE PHOENIX
A wonderful and authoritative collection of old Jewish legends: The Book of Legends, Sefer Ha-Aggadah: Legends from the Talmud and Midrash (1999). H. N. Bialik, editor; W. Braude, translator. Schocken.
For reviews of Denham Harman’s thinking about aging, see:
Harman, D. (2006). “Free radical theory of aging: an update,” Ann NY Acad Sci 1067: 10–21.
Kitani, K., and G. O. Ivy (2003). “‘I thought, thought, thought for four months in vain and suddenly the idea came.’ Interview with Denham and Helen Harman.” Biogerontology 4: 401–12.
de Grey, A. D. (1997). “A proposed refinement of the mitochondrial free radical theory of aging.” Bioessays 19(2): 161–66.
de Grey, A. D. (2002). “Three detailed hypotheses implicating oxidative damage to mitochondria as a major driving force in homeotherm aging.” Eur J Biochem 269(8): 1995.
CHAPTER 5: THE EVOLUTION OF AGING
Peter Medawar’s key essays about the evolution of aging are reprinted in:
Medawar, P. (1981). The Uniqueness of the Individual. Dover.
He returns to the subject in his quirky autobiography:
Medawar, P. (1988). Memoir of a Thinking Radish. Oxford University Press.
And again in:
Medawar, P. (1990). The Threat and the Glory. HarperCollins.
See also:
Finch, C. E., and E. M. Crimmins (2004). “Inflammatory exposure and historical changes in human life-spans.” Science 305(5691): 1736–39.
Caspari, R., and Lee, S.-H. (2004). “Older age becomes common late in human evolution.” PNAS 101(30): 10895–10900.
Crespi, B. J. (2004). “Vicious circles: Positive feedback in major evolutionary and ecological transitions.” TREE 19(12): 627–33.
Rose, M. R. (1991). Evolutionary Biology of Aging. Oxford University Press.
Stearns, S. C., and J. C. Koella (2008). Evolution in Health and Disease. Oxford University Press.
Platt, R. (1963). “Reflections on ageing and death.” Lancet. 281: 1–6.
CHAPTER 6: THE GARBAGE CATASTROPHE
Holliday, R. (2006). “Aging is no longer an unsolved problem in biology.” Ann NY Acad Sci 1067: 1–9.
de Grey, A. D. (2007). “Alzheimer’s, atherosclerosis, and aggregates: A role for bacterial degradation.” Nutr Rev 65(12 Pt 2): S221–27.
Terman, A., and U. T. Brunk (2006). “Oxidative stress, accumulation of biological ‘garbage,’ and aging.” Antioxid Redox Signal 8(1–2): 197–204.
Stroikin, Y., H. Dalen, et al. (2005). “Testing the ‘garbage’ accumulation theory of ageing: mitotic activity protects cells from death induced by inhibition of autophagy.” Biogerontology 6(1): 39–47.
CHAPTER 7: THE SEVEN DEADLY THINGS
For a full-length treatment of de Grey’s Strategies for the Engineering of Negligible Senescence, see his book Ending Aging (op cit.).
He’s also published dozens of shorter accounts, including:
de Grey, A. D. (2005). “A strategy for postponing aging indefinitely.” Stud Health Technol Inform 118: 209–19.
For Michael Hecht’s experiments with beta-amyloid:
Kim, W., Y. Kim, et al. (2006). “A high-throughput screen for compounds that inhibit aggregation of the Alzheimer’s peptide.” ACS Chem Biol 1(7): 461–69.
Kim, W., and M. H. Hecht (2008). “Mutations enhance the aggregation propensity of the Alzheimer’s A beta peptide.”
J Mol Biol 377(2): 565–74.
de Grey, A. D., P. J. Alvarez, et al. (2005). “Medical bioremediation: prospects for the application of microbial catabolic diversity to aging and several major age-related diseases.” Ageing Res Rev 4(3): 315–38.
CHAPTER 8: THE METHUSELAH WARS
For a meticulously detailed contemporary history, see Hall, S. (2003). Merchants of Immortality: Chasing the Dream of Human Life Extension. Houghton Mifflin.
Klass, M. R. (1983). “A method for the isolation of longevity mutants in the nematode Caenorhabditis elegans and initial results.” Mech Ageing Dev 22(3–4): 279–86.
Klass, M., and D. Hirsh (1976). “Non-ageing developmental variant of Caenorhabditis elegans.” Nature 260(5551): 523–25.
Kenyon, C., J. Chang, et al. (1993). “A C. elegans mutant that lives twice as long as wild type.” Nature 366(6454): 461–64.
Kenyon, C. (2005). “The Plasticity of Aging: Insights from Long-Lived Mutants.” Cell 120: 449–60.
Song, S., and T. Finkel (2007). “GAPDH and the search for alternative energy.” Nature Cell Biology 9(8): 869–70.
Zhang C., and A. M. Cuervo (2008). “Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function.” Nat Med 14(9): 959–65.
Kaushik S., and A. M. Cuervo (2008). “Chaperone-mediated autophagy.” Methods Mol Biol 445:227–44.
Cuervo, A. M. (2008). “Autophagy and aging: Keeping that old broom working.” Trends Genet 24: 604–12.
Cuervo, A. M., L. Stefanis, et al. (2004). “Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy.” Science 305: 1292–95.
Mizushima N., B. Levine, et al. (2008). “Autophagy fights disease through cellular self-digestion.” Nature 451:1069–75.
Hansen, M., A. Chandra, et al. (2008). “A role for autophagy in the extension of lifespan by dietary restriction in C. elegans.” PLoS Genet 4(2): e24.
Rubinsztein, D. C., J. E. Gestwicki, et al. (2007). “Potential therapeutic applications of autophagy.” Nat Rev Drug Discov 6(4): 304–12.
Sarkar, S., E. O. Perlstein, et al. (2007). “Small molecules enhance autophagy and reduce toxicity in Huntington’s disease models.” Nat Chem Biol 3(6): 331–38.
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